Your Digest for Saturday, Sep 30, 2023 10:59 PM


#2020BSQ-NOV/Q10
#2020BSQ-NOV/Q20

Carbimazole / methimazole Propylthiouracil
Less severe side effects. Usually first line choice Usually second line, except T1 of pregnancy, <- preferred in T1
and thyroid storm
Blocks 5'-monodeiodinase, which converts peripheral T4 to T3 conversion
Less frequent teratogenic effects
Pruritus, rash, arthritis, urticaria, abnormal taste Same
Agranulocytosis (0.1% incidence) Same
Less risk of hepatic injury (?can cause cholestatis) Fulminant hepatic failure
ANCA positive vasculitis

Adverse drug reactions

#2020BSQ-NOV/Q18

Adverse drug reaction: A noxious and unintended response to a drug that occurs during usual clinical use.

Adverse drug event: any unexpected or inappropirate occurence that occurs during drug administration. Does not necessarily have a causal relationship to the drug administration.

Intentional overdose and prescribing errors are not adverse drug reactions.

What is meant by idiosyncratic:

Drug idiosyncrasy—A genetically determined, qualitatively abnormal reaction to a drug related to a metabolic or enzyme deficiency
(i.e when some patient factor interacts with drug pharmacology to create the adverse reaction).

Type Description Comments Example
Type A Augmented - Dose dependent Can occur at normal or abnormal doses Serotonin syndrome, bleeding with heparin etc.
B Bizarre - non dose related Any exposure is enough to tigger the reaction Anaphylaxis, idiosyncratic reactions
C Chronic - dose and time related Occurs due to dose accumulation Adrenal suppresion with corticosteroids
D Delayed - time related Due prolonged use without dose accumulation tardive dyskinseia with atypical antipsychotics
E End of use Adverser events on withdrawa Opiate withdrawal, rebound hypertension with clonidine
F Failure Undesirable reduction in drug efficacy Like drug efficacy reduced by dialysis

Effective renal plasma flow can be calculated using the Fick principle with para-amino hippuric acid. This is a substance that is filtered and secreted by the kidney (but not reabsorbed) meaning that almost all of it is removed in a pass through the kidney. (extraction ratio is around 90%).


#2020BSQ-NOV/Q02

It is the most common cause of lactase deficiency, also known as lactase non-persistence. There is a gradual decline in lactase enzyme activity with increasing age. Enzyme activity begins to decline in infancy, and symptoms manifest in adolescence or early adulthood.

Secondary Lactase Deficiency
Due to several infectious, inflammatory, or other diseases, injury to intestinal mucosa can cause secondary lactase deficiency. Common causes include:


Types of cellular receptors

There are 4 types of receptors:

  1. Ligand gated ion channels: timescale is milliseconds
    1. role: fast neutrotransmitters :
  2. G-protein coupled receptors ("7 transmembrane receptors): timescale is seconds.
    1. Largest family of receptors; "metabotropic";
    2. hormone receptors and slow transmitters;
  3. Kinase linked and kinase related receptors: timescale - hours
    1. heterogenous group; triggered by protein mediators.
    2. They have a single transmembrane domain. Intracellular transduction is mediated by a protein kinase or guanyl cylcase.
      1. Guanyl cyclase is an enzyme which catalyzes the synthesis of cyclic guanosine 3′,5′-monophosphate (cGMP)
  4. Nuclear receptors: Timescale - Hours
    1. They regulate gene transcriptions.
      typesOfReceptors.png
      propertiesOfRecetorTypes.png

G protein coupled receptors (GPCR)

[!TIP]
This Source is very good and agrees with Rang and Dale but is much shorter and is the source for all the images.

GPCRSummary.png
GPCRs.png
Incredibly short overview:

cAMP (cyclic AMP)

cAMPPathway.png

Phospholipase C / inositol triphosphate / diacylglycerol

phospholipaseIP3DAGpathway.png

Ligand gated ion channels GPCR Receptor Kinases Nuclear receptors
Muscarinic ACh receptors
[[adrenoceptors.png|Adrenoceptors]]
Dopamine receptor
5-HT receptor
Chemoreceptors in the nose
opioid
Cannabinoid
Catecholamines, histamines, serotonine

[!TIP]
The nitocinic receptors (which is a ligand gated ion channel) is found at the neuromusclar junction.

Tyrosine kinases

Adenylyl cyclase and cAMP system

One of the targets of G proteins.


Alveolar arterial oxygen gradient increases in CO poisoning.


Antipseudomonal carbapenems – imipenem, meropenem and doripenem – have excellent activity against most strains of many bacterial species and are regarded as safe and generally well-tolerated. Of note, these carbapenems are resistant to ESBLs, and so are of value in treating infections caused by ESBL-producing strains of Enterobacteriaceae
Source

#2020BSQ-NOV/Q19


Pharmacokinetics overview

[!INFO] Pharmacokinetics Vs. Pharmacodynamics
Dynamics = 'power'
Pharmacodynamics = effect drugs have on the body.
Pharmacokinetics = effect body has on drug concentrations.

Bioavailability

#2020BSQ-NOV/Q17

$$
Bioavailability=\frac{AUC_{oral}}{AUC_{IV}}
$$
where AUC = area under the curve for drug concentration Vs. time graph.

Effect of liver failure on pharmacokinetics

Mathematics of hepatic pharmacokinetics

Source

[!INFO]
Extraction ratio : Hepatic extraction ratio ... is the fraction of the drug entering the liver in the blood which is irreversibly removed (extracted) during one pass of the blood through the liver.
$$
\large Extraction\space Ratio = \frac{C_{arterial} - C{venous}}{C_{arterial}}
$$
Protein binding affects hepatic extraction ratio because hepatocytes have access only to the unbound form of the drug.
Therefore, the equation above is equivalently represented as
$$
\large E_H = \frac{fu\times Cl_{int}}{Q_{H}+fu\times Cl_{int}}
$$

  1. Hepatic blood flow
  2. Unbound fraction of the drug
  3. Intrinsic ability of the liver to metabolize the drug

[!INFO] The upshot
Drugs with low intrinsic clearance will have "intrinsic limited" clearance
Drugs with high intrinsic clearance will have "flow limited" clearance.

Effects in liver failure

In liver failure,


The A-a gradient tends to increases with age.
(A-a gradient = 2.5 + FiO2 x age in years<-- Source )

Of the 5 causes of hypoxaemia, elevated A-a gradient excludes hypoventilation and low FiO2 as the causes.
The 5 causes must be written down somewhere else but just in case:

  1. V/Q mismatch, R->L shunt, Diffusion impairement, Low FiO2, hypoventilation)

Increased in

Normal in

Source
alveolarArterialOxygenGradient.png


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